Key result
Lower VCANM levels during acute IIP exacerbations linked to increased mortality risk.
Why the study?
Idiopathic interstitial pneumonia involves increased extracellular matrix remodeling during acute exacerbations, but the relationship between ECM remodeling biomarkers and mortality is unclear.
Do serological biomarkers of extracellular matrix remodeling, specifically versican degradation (VCANM), predict mortality in patients with acute exacerbations of idiopathic interstitial pneumonia?
Observational (n=97)
No
Do serological biomarkers of extracellular matrix remodeling, specifically versican degradation (VCANM), predict mortality in patients with acute exacerbations of idiopathic interstitial pneumonia?
Lower serum levels of versican degradation (VCANM) during acute exacerbations of idiopathic interstitial pneumonia are associated with an increased risk of mortality, suggesting its potential as a prognostic biomarker.
Lower VCANM at AE-IIP was associated with higher mortality; leaves open whether versican degradation biomarkers aid prognostic stratification in IIP exacerbations.
BACKGROUND: Idiopathic interstitial pneumonia (IIP) is characterized by an increased rate of extracellular matrix (ECM) remodeling resulting in fibrosis. Acute exacerbations of IIP represent periods of increased disease activity, thus we hypothesized that ECM remodeling was altered during acute exacerbations and investigated this by serological neo-epitope biomarkers. METHODS: Patients who were sequentially admitted to the hospital with acute exacerbations of IIP were retrospectively analyzed for ECM remodeling at time of exacerbation (AE-IIP) and at clinical stability (S-IIP). Biomarkers released by matrix metalloproteinase-mediated degradation of collagen type I (C1M), III (C3M), IV (C4M), and VI (C6M), elastin (ELM7), versican (VCANM), biglycan (BGM), and C-reactive protein (CRPM) were assessed in serum by competitive ELISAs utilizing neo-epitope specific monoclonal antibodies. RESULTS: Sixty-eight patients at AE-IIP and 29 at S-IIP were included in this retrospective analysis. Of these, 28 and 11 patients, respectively, had idiopathic pulmonary fibrosis. At AE-IIP, serum levels of C4M (p = 0.002) and C6M (p = 0.024) were increased as compared with S-IIP, while ELM7 (p = 0.024) and VCANM (p < 0.0001) were decreased. Lower VCANM levels at AE-IIP were associated with increased risk of mortality (HR 0.64 [95% CI 0.43-0.94], p = 0.022). CONCLUSIONS: The ECM remodeling profile was significantly altered during acute exacerbations of IIP, and a biomarker of versican degradation was related to mortality outcome. These results indicate that biomarkers of ECM remodeling may be useful in the non-invasive evaluation of acute exacerbations of IIP. Especially versican degradation, as measured serologically by VCANM, may have prognostic potential and help guide treatment for acute exacerbations.
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Sand et al. (2018) conducted an observational in Idiopathic Interstitial Pneumonia (n=97). Serum VCANM levels vs. Higher VCANM levels was evaluated on Mortality (HR 0.64, 95% CI 0.43-0.94, p=0.022). Lower serum levels of the versican degradation biomarker VCANM during acute exacerbations of idiopathic interstitial pneumonia were associated with an increased risk of mortality (HR 0.64).
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